基于分子对接结合靶标mRNA表达的交泰丸镇静催眠药效物质及机制研究  

Study on Mechanism and Sedative-hypnotic Substances in Jiaotai Pills Based on Molecular Docking and Target mRNA Expression

作　　者：韩洪翠 张艳玲 路芳[1] 毕磊 黄运芳 马鹏凯[1] 张玉杰[1] HAN Hongcui;ZHANG Yanling;LU Fang;BI Lei;HUANG Yunfang;MA Pengkai;ZHANG Yujie(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China)

机构地区：[1]北京中医药大学中药学院,北京102488

出　　处：《中国中医药信息杂志》2021年第3期57-62,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(81673680)。

摘　　要：目的运用分子对接技术与靶标mRNA表达相结合方法,探索交泰丸治疗失眠症药效物质及分子作用机制。方法选择5-羟色胺1A(5-HT1A)受体、γ-氨基丁酸(GABAA)受体、多巴胺D3(DRD3)受体作为对接蛋白靶标,将其分别与交泰丸中主要黄连生物碱进行分子对接,明确各成分与靶标结合的强度;腹腔注射对氯苯丙胺酸建立小鼠失眠症模型,并分别予小檗碱(BBR)、黄连碱(COP)、巴马汀(PAL)、表小檗碱(EBBR)、药根碱(JAT)5种生物碱灌胃,连续7 d,测定小鼠脑组织5-HT1A受体、GABAA受体α1亚型(Gabra1)受体和DRD3受体的mRNA表达。结果以5-HT1A为分子靶标,各配体对接评分顺序为EBBR>阿米替林>COP>BBR>PAL>JAT;以GABAA为分子靶标,对接评分顺序为COP>BBR>EBBR>PAL>JAT>巴比妥;以DRD3为分子靶标,对接评分顺序为BP-897>EBBR>PAL>COP>JAT>BBR。与模型组比较,除COP对DRD3表达上调不明显外,各给药组5-HT1A、Gabra1和DRD3 mRNA表达均显著上调(P<0.05,P<0.01)。结论原小檗碱型生物碱是交泰丸主要药效成分,其中小檗碱作用最强;交泰丸治疗失眠症的机制可能是通过调节5-HT_(1A)、Gabra1、DRD3等受体的表达完成。Objective To explore the effective substances and the molecular mechanism of insomnia treatment of Jiaotai Pills using the method of molecular docking technology and target mRNA expression.Methods 5-HT1A,GABAA and DRD3 were selected as docking protein targets respectively for molecular docking with the main Coptis alkaloids in Jiaotai Pills and the binding strength of each component to the targets were determined.The insomnia model of mice was established by intraperitoneal injection of p-chloroamphetamine.BBR,COP,PAL,EBBR,JAT five of Coptis alkaloids were administrated to mice for 7 days.The mRNA expressions of 5-HT1A,Gabra1 and DRD3 in mice brain were measured.Results With 5-HT1A as the molecular target,the docking score order of each ligand was EBBR>Amitriptyline>COP>BBR>PAL>JAT;with GABAA as the molecular target,the docking score order was COP>BBR>EBBR>PAL>JAT>Barbital;with DRD3 as the molecular target,the docking score order was BP-897>EBBR>PAL>COP>JAT>BBR.Compared with the model group,the mRNA expressions of 5-HT1A,Gabra1 and DRD3 significantly increased in the administration groups(P<0.05,P<0.01),except that the expression of DRD3 was not significantly up-regulated by COP.Conclusion Protoberberine alkaloids are the main effective substances of Jiaotai Pills,among which berberine has the strongest effect.Jiaotai Pills might treat insomnia by regulating the expressions of 5-HT_(1A),Gabra1,DRD3 and other receptors。

关 键 词：分子对接 交泰丸 黄连生物碱 镇静催眠 5-羟色胺1A受体 多巴胺D3受体 γ-氨基丁酸受体α1亚型 小鼠 

分 类 号：R285.5[医药卫生—中药学]